Specifically, the study described in this proposal will test the hypothesis that the increase in tuberculosis in San Francisco is largely due to "facilitated" transmission of M. tuberculosis in definable settings which have high tuberculosis prevalence and large numbers of individuals with impaired immunity. We will continue to use restriction fragment length polymorphism (RFLP) analysis, with which we have demonstrated the ability to identify individuals strains of M. tuberculosis (Daley, Small, et. al. N. Eng J. Med), to identify residents of San Francisco who are infected with the same strains. Detailed epidemiologic investigation of these individuals will be conducted to determine where they contracted tuberculosis, thus defining the specific environments in the city that foster tuberculosis transmission. Further investigation of the patients involved will be conducted to determine the modifiable risk factors for the acquisition of tuberculosis. Ultimately, this information will permit the design of more effective prevention strategies. RFLP analysis is a powerful epidemiologic tool. However, because culturing bacteria is a prerequisite for its use, it is limited to culture positive cases and results are not available for 4-6 weeks after a specimen is collected. In order to eliminate this delay we plan to design and validate a polymerase chain reaction (PCR) based fingerprinting system. This system will be optimized and validated on DNA, which will have been extracted and characterized in previous RFLP- based molecular epidemiologic studies.